Alkaline Hydrolysis of the Cytostatic Drug,Ifosfamide, and its N-Dechloroethylated Metabolites

Abstract

I fosfamide (IF) is an alkylating antitumor agent used in the treatment of solid tumors. Up to 50% of IF administered to patients undergoes an oxidative N-dealkylation reaction resulting in the loss or one, other or both chloroethyl side chain(s) to produce 2- or 3-dechloioethylIF (ZDCIF, 3DCIF) or 2,3-didechloroethyllF (DDCIF). The hydrolytic pathway of these four oxazaphosphorines has been studied earlier but only at acidic and neutral pHs^l] In the present work, we monitored their time courses of hydrolysis at basic pHs using phosphorus-3 1 NMR. The structures of the compounds formed were determined by NMR (13C and 1H) and mass spectrometry. The results are reported in the following scheme.